Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact ...of NRP on the short‐term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012–2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high‐volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p = .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 95% CI 1.43–2.72; p < .001) and 1‐year graft loss (OR 1.77 95% CI 1.01–3.17; p = .034). In conclusion, compared with RR, NRP appears to improve the short‐term outcomes of cDCDD kidney transplants.
This multicenter, nationwide, retrospective study that uses propensity score matching shows lower delayed graft function and higher 1‐year graft survival rates for transplants using kidneys from controlled donation after circulatory determination of death donors procured with normothermic regional perfusion versus through rapid recovery.
Heart transplantation from controlled donation after the circulatory determination of death (cDCDD) may help to increase the availability of hearts for transplantation. During 2020, four heart ...transplants were performed at three different Spanish hospitals based on the use of thoraco‐abdominal normothermic regional perfusion (TA‐NRP) followed by cold storage (CS). All donors were young adults <45 years. The functional warms ischemic time ranged from 8 to 16 minutes. In all cases, the heart recovered sinus rhythm within 1 minute of TA‐NRP. TA‐NRP was weaned off or decreased <1L within 25 minutes. No recipient required mechanical support after transplantation and all were immediately extubated and discharged home (median hospital stay: 21 days) with an excellent outcome. Four livers, eight kidneys, and two pancreata were also recovered and transplanted. All abdominal grafts recipients experienced an excellent outcome. The use of TA‐NRP makes heart transplantation feasible and allows assessing heart function before organ procurement without any negative impact on the preservation of abdominal organs. The use of TA‐NRP in cDCDD heart donors in conjunction with cold storage following retrieval can eliminate the need to use ex situ machine perfusion devices, making cDCDD heart transplantation economically possible in other countries.
Heart transplantation from controlled donation after circulatory determination of death using thoraco‐abdominal normothermic regional perfusion followed by cold storage after retrieval is feasible and may reduce the need for ex situ machine perfusion.
Background and Aims
Hepatic ischemia–reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage ...of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation‐controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models.
Approach and Results
Wild‐type (WT), MCJ knockout (KO), and Mcj silenced WT mice were subjected to 70% partial hepatectomy (Phx), prolonged IRI, and 70% Phx with IRI. Old and young mice with metabolic syndrome were also subjected to these procedures. Expression of MCJ, an endogenous negative regulator of mitochondrial respiration, increases in preclinical models of Phx with or without vascular occlusion and in donor livers. Mice lacking MCJ initiate liver regeneration 12 h faster than WT and show reduced ischemic injury and increased survival. MCJ knockdown enables a mitochondrial adaptation that restores the bioenergetic supply for enhanced regeneration and prevents cell death after IRI. Mechanistically, increased ATP secretion facilitates the early activation of Kupffer cells and production of TNF, IL‐6, and heparin‐binding EGF, accelerating the priming phase and the progression through G1/S transition during liver regeneration. Therapeutic silencing of MCJ in 15‐month‐old mice and in mice fed a high‐fat/high‐fructose diet for 12 weeks improves mitochondrial respiration, reduces steatosis, and overcomes regenerative limitations.
Conclusions
Boosting mitochondrial activity by silencing MCJ could pave the way for a protective approach after major liver resection or IRI, especially in metabolically compromised, IRI‐susceptible organs.
The aim of this study was to compare the outcomes of lung transplantations using grafts from donors aged over 70 years against those performed using younger donors.
This retrospective single-centre ...analysis includes lung transplants conducted at our institution from January 2014 to June 2022. Lung recipients were classified into 2 groups based on donor age (group A <70 years; group B ≥70 years). Variables regarding demographics, peri and postoperative outcomes and survival were included. The statistical analysis approach included univariable analysis, propensity score matching to address imbalances in donor variables (smoking status), recipient characteristics (sex, age, diagnosis and lung allocation score) and calendar period and survival analysis.
A total of 353 lung transplants were performed in this period, 47 (13.3%) using grafts from donors aged over 70 years. Donors in group B were more frequently women (70.2% vs 51.6%, P = 0.017), with less smoking history (22% vs 43%, P = 0.002) and longer mechanical ventilation time (3 vs 2 days, P = 0.025). Recipients in group B had a higher lung allocation score (37.5 vs 35, P = 0.035). Postoperative variables were comparable between both groups, except for pulmonary function tests. Group B demonstrated lower forced expiratory volume 1 s levels (2070 vs 2580 ml, P = 0.001). The propensity score matching showed a lower chance of chronic lung allograft dysfunction by 12% for group B. One-, three- and five-year survival was equal between the groups.
The use of selected expanded-criteria donors aged over 70 years did not result in increased postoperative morbidity, early mortality or survival in this study.
Abstract
OBJECTIVES
Controlled donation after circulatory death (cDCD) donors are becoming a common source of organs for transplantation globally. However, the graft survival rate of cDCD abdominal ...organs is inferior to that of organs from brain-dead donors. The rapid retrieval (RR) technique is used by most donor organ procurement teams. The abdominal normothermic regional perfusion (A-NRP) technique has been implemented to minimize warm ischaemic damage to the abdominal organs. However, there is limited information on the effect of A-NRP on the quality of the donor lungs. This study aimed to compare lung transplantation outcomes using lungs procured from cDCD donors using the A-NRP and abdominal RR techniques.
METHODS
A single-centre retrospective analysis of consecutive transplant recipients of cDCD lungs from June 2013 to December 2019 was performed. The recipients were divided into 2 cohorts according to the abdominal procurement technique used. The recipient and donor characteristics (age, sex, cause of brain injury, warm ischaemic time, diagnosis, lung allocation score and other factors), incidence of primary graft dysfunction and early survival were monitored.
RESULTS
Twenty-eight consecutive lung transplantation recipients were identified (median age 59 years; 61% male); 14 recipients received lungs using the A-NRP and 14 using abdominal RR for abdominal organ retrieval. There were no significant differences in the baseline characteristics, primary graft dysfunction (P = 0.70), hospital mortality (P = 1.0) and 1-year survival rate (P = 1.0) between the 2 groups.
CONCLUSIONS
No difference was observed in lung transplantation outcomes irrespective of the abdominal organ procurement technique used (A-NRP or abdominal RR).
Lung transplantation (LTx) is an established therapy for end-stage lung disease in selected patients; however, it is limited by the shortage of donor organs 1.
Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially ...increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72 h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor’s plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.
Summary
Controlled donation after circulatory death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are ...sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). This is a retrospective analysis of all LTx performed between January 2013 and December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 h, 30‐ and 90‐day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7% respectively; P = 0.42). Short‐ and mid‐term outcomes are comparable between the three types of donors. These findings may encourage and reinforce all types of donation after circulatory death programmes as a valid and growing source of suitable organs for transplantation.
Lung transplantation from uncontrolled and controlled donors after circulatory death offers similar outcomes to brain death donors in terms of early and mid‐term results. Overall survival and CLAD‐free survival at 1 and 3 years are comparable between the three types of donors.
To better define the risk of malignancy transmission through organ transplantation, we review the Spanish experience on donor malignancies.
We analyzed the outcomes of recipients of organs obtained ...from deceased donors diagnosed with a malignancy during 2013-2018. The risk of malignancy transmission was classified as proposed by the Council of Europe.
Of 10 076 utilized deceased donors, 349 (3.5%) were diagnosed with a malignancy. Of those, 275 had a past (n = 168) or current (n = 107) history of malignancy known before the transplantation of organs into 651 recipients. Ten malignancies met high-risk criteria. No donor-transmitted cancer (DTC) was reported after a median follow-up of 24 (interquartile range IQR: 19-25) mo. The other 74 donors were diagnosed with a malignancy after transplantation. Within this group, 64 donors (22 with malignancies of high or unacceptable risk) whose organs were transplanted into 126 recipients did not result in a DTC after a median follow-up of 26 (IQR: 22-37) mo, though a prophylactic transplantectomy was performed in 5 patients. The remaining 10 donors transmitted an occult malignancy to 16 of 25 recipients, consisting of lung cancer (n = 9), duodenal adenocarcinoma (n = 2), renal cell carcinoma (n = 2), extrahepatic cholangiocarcinoma (n = 1), prostate cancer (n = 1), and undifferentiated cancer (n = 1). After a median follow-up of 14 (IQR: 11-24) mo following diagnosis, the evolution was fatal in 9 recipients. In total, of 802 recipients at risk, 16 (2%) developed a DTC, which corresponds to 6 cases per 10 000 organ transplants.
Current standards may overestimate the risk of malignancy transmission. DTC is an infrequent but difficult to eliminate complication.
Controlled donation after circulatory death (cDCD) has emerged as one of the main strategies for increasing the organ donor pool. Because of the ischemic injury that follows the withdrawal of ...life-sustaining therapies, hearts from cDCD donors have not been considered for transplantation until recently. The ex-situ perfusion of hearts directly procured from cDCD donors has been used to allow the continuous perfusion of the organ and the assessment of myocardial viability prior to transplantation. Based on our experience with abdominal normothermic regional perfusion in cDCD, we designed a protocol to recover and validate hearts from cDCD donors using thoraco-abdominal normothermic regional perfusion without the utilization of an ex-situ device.
We describe the first case of a cDCD heart transplant performed with this approach in Spain. The donor was a 43-year-old asthmatic female diagnosed with severe hypoxic encephalopathy. She was considered a potential cDCD donor and a suitable candidate for multiorgan procurement including the heart via thoraco-abdominal normothermic regional perfusion. The heart recipient was a 60-year-old male diagnosed with amyloid cardiomyopathy. Cold ischemia time was 55 min. The surgery was uneventful.
This case report, the first of its kind in Spain, supports the feasibility of evaluating and successfully transplanting cDCD hearts without the need for ex-situ perfusion based on the use of thoraco-abdominal normothermic regional perfusion opening the way for multiorgan donation in cDCD.
Abstract
OBJECTIVES
Bronchial anastomotic complications remain a major concern in lung transplantation. We aim to compare 2 different techniques, continuous suture (CS) versus interrupted suture (IS) ...by analysing airway complications requiring intervention.
METHODS
Lung transplantations between January 2015 and December 2020 were included. Airway complications requiring intervention were classified following the 2018 International Society for Heart and Lung Transplantation consensus and analysed comparing 3 groups of patients according to surgical technique: group A, both anastomosis performed with CS; group B, both with interrupted; and group C, IS for 1 side and CS for the contralateral side.
RESULTS
A total of 461 anastomoses were performed in 245 patients. The incidence of airway complications requiring intervention was 5.7% 95% confidence interval (CI): 2.8–8.6 per patient (14/245) and 3.7% (95% CI: 2.0–5.4) per anastomosis (17/461). Complications that required intervention were present in 5 out of 164 (3.1%) anastomosis with interrupted technique, and in 12/240 (5%) with CS. No significant differences were found between techniques (P = 0.184). No statistical differences were found among group A, B or C in terms of incidence of anastomotic complications, demographics, transplant outcomes or overall survival (log-rank P = 0.513). In a multivariable analysis, right laterality was significantly associated to complications requiring intervention (OR 3.7 95% CI: 1.1–12.3, P = 0.030). Endoscopic treatment was successful in 12 patients (85.7%). Retransplantation was necessary in 2 patients.
CONCLUSIONS
In summary, although it seems that anastomotic complications requiring intervention occur more frequently with CS, there are no statistical differences compared to IS. Endoscopic treatment offers good outcomes in most of the airway complications after lung transplantation.
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